RSV presents a significant cause of morbidity in the very young and elderly and there is currently no licensed vaccine to prevent RSV infection. The induction of both protective, disease-sparing CD8+ T cell responses and protective neutralizing antibodies are desirable in a vaccine candidate. These studies are designed to identify interventions that will increase the efficiency of nucleic acid and vector-based immunization and to optimize the conditions of each intervention. The magnitude and the quality of the immune responses induced by each vector will be compared using murine prime-challenge models. We have characterized numerous gene-based delivery vectors that express the wild-type RSV F protein. In another project Antigenicity and Immunogenicity of Stablized prefusion F protein, we have stabilized the RSV F protein in the prefusion conformation (Pre-F) and characterized the antigenicity and immunogenicity of the Pre-F protein. Currently, we are comparing vaccine regimens using DNA plasmids and gorilla adenovirus vectors expressing either the stabilized Pre-F protein or the wildtype F protein to vaccination with soluble Pre-F protein. We are also working with collaborators to assess immunogenicity of other vectors expressing our stabilized Pre-F protein.